Bivalent Binding of IgA1 to FcαRI Suggests a Mechanism for Cytokine Activation of IgA Phagocytosis
Abstract
FcαRI, the receptor specific for the Fc region of immunoglobulin A (IgA), is responsible for IgA-mediated phagocytosis, oxidative burst, and antibody-dependent cellular cytotoxicity. Using the techniques of analytical ultracentrifugation and equilibrium gel-filtration, we show that two FcαRI molecules bind to a single Fcα homodimer. Surface plasmon resonance studies confirm the 2:1 stoichiometry of binding, with equilibrium dissociation constants of 176 nM and 431 nM for the first and second binding events, respectively. The binding affinity decreases at acidic pH in a manner consistent with protonation of a single histidine residue in the binding site. A thermodynamic analysis indicates that the histidine residue does not participate in a salt-bridge in the complex; in fact, less than 10% of the free energy of binding was contributed by electrostatic interactions. The bivalent, pH-dependent interaction between FcαRI and IgA has important implications for cytokine-dependent phagocytosis of IgA and the FcαRI-mediated degradation or recycling of IgA.
Additional Information
© 2003 Elsevier Science Ltd. Received 23 July 2002; received in revised form 16 January 2003; accepted 24 January 2003. We thank Anthony West, Anthony Giannetti, and Benjamin Willcox for advice on biosensor experiments; Peter Snow and Inderjit Nangiana (Caltech Protein Expression Facility) for FcαRI expression; and Michael Bradshaw and members of the Bjorkman laboratory for critical reading of the manuscript. N-terminal sequencing analysis was carried out at the Caltech Protein/Peptide Micro Analytical Laboratory (PPMAL) under the direction of Gary M. Hathaway. This work was supported by the Howard Hughes Medical Institute (to P.J.B.), and fellowships DRG-1658 (to A.B.H.) and DRG-1385 (to C.L.W.) of the Damon Runyon Cancer Research Foundation.Additional details
- Eprint ID
- 75427
- Resolver ID
- CaltechAUTHORS:20170327-135508111
- Howard Hughes Medical Institute (HHMI)
- Damon Runyon-Walter Winchell Cancer Research Foundation
- DRG-1658
- Damon Runyon-Walter Winchell Cancer Research Foundation
- DRG-1385
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2017-03-27Created from EPrint's datestamp field
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2021-11-15Created from EPrint's last_modified field